Because clonal expansion (i.e. proliferation of specific activated B Cells after exposure to a foreign antigen) is a slow process, our first line of defense is our Innate Immune System.

Acquired and innate immune mechanisms communicate and regulate each other.

Example: Macrophages

Þ IL-12 Þ Shift of T cell differentiation from TH2 to TH1.

Innate immune mechanisms are not "specific" in the immunological sense, but they rely on events that are biochemically specific

Example: Receptors bind LPS from a bug in a manner that is biochemically specific, and this may trigger the release of cytokines and start an innate immune response. LPS is not a unique antigen but rather a wall component of all Gram-negative bugs.

a  activates vascular endothelium and increases vascular permeability, which leads to increased entry of IgG, complement, and cells and increased fluid drainage to lymph nodes

Systemic effects: Fever, Mobilization of metabolites, Shock

Note: When TNF-

a is secreted in tissues it just has its permeability-inducing affects on local vasculature, when it is secreted into the circulation this affect will devastate the system by causing systemic edema, decreased blood volume, and hypoproteinemia, leading to intravascular coagulation, wasting, and multiple organ failure.

(4) IL-6

 lymphocyte activation, increased antibody production

Systemic effects: Fever, induces acute-phase protein production by telling hepatocytes to make more proteins which help phagocytosis (ex: c-reactive protein, mannnan-binding lectin)

 upon detection of double stranded RNA (i.e. bacterial) there is increased production of IFN-a , IFN-b , TNF-a , and IL-12. This induces NK-cell mediated killing of infected cells, and starts the process of priming T-Cells.

NK cells

 viruses can interfere with the production of MHC and thus avoid detection. The Immune System uses NK cells to detect this down-regulation of MHC class-1 proteins by the virus. When the NK cell detects this low level of MHC it attacks! This mechanism is normally used as negative-feedback. The MHC (class 1 ONLY) is detected, which signals to NK cells that everything is kosher.

Example of Innate Immunity

A wound penetrating the epithelium allows bugs to get in. Defensins (antibacterial proteins) insert into bugs and start killing them, complement proteins attach to bugs, phagocytes (macrophages and PMNs) rush to the scene, and NK cells start doing their thing